“To the best of our knowledge, this is the largest prospective study on recurrent events in hypercoagulable patients with PFO associated embolism,” the authors, led by Kai Liu, MD, Massachusetts General Hospital, Boston, write.
The study is published in the December 14 issue of JACC: Cardiovascular Interventions.
They explain that randomized controlled trials have shown PFO closure to be superior to medical therapy in reducing recurrent stroke or transient ischemic attack (TIA) in patients with no other known cause of ischemic stroke. But these studies have excluded many potentially high-risk patients with thrombophilia (hypercoagulable state), who are at increased risk of recurrent events and are currently treated with anticoagulation.
“Thus far, there has been little beside clinical experience to guide treatment of patients with PFO stroke with thrombophilia,” they note.
They estimate that the combination of a hypercoagulable state and PFO has a prevalence of 5% to 31%, and the presence of the two conditions may increase the risk for stroke.
The current study involved 591 patients with cryptogenic stroke attributed to PFO, of whom 134 patients (22.7%) were identified as having least one thrombophilia abnormality.
An interdisciplinary PFO committee evaluated the appropriateness of PFO closure for each patient. Patients received aspirin (81 or 325 mg/day) and/or clopidogrel (75 mg/day) at the discretion of the operator. Those who had thrombophilia and a single embolism were anticoagulated with warfarin for 3 months with a target international normalized ratio between 2 and 3 and then switched to aspirin. Patients with 2 or more embolic events were anticoagulated with lifelong warfarin therapy.
The median duration of follow-up was 53 months. Results showed that patients with thrombophilia had a significantly increased risk for recurrent events (hazard ratio [HR] 1.85; P = .024).
“Thus, comprehensive hypercoagulation testing should be considered in patients with PFO-attributable cryptogenic embolism, which may identify patients with high risk for recurrence,” the authors comment.
PFO closure was superior to medical therapy in patients overall (HR, 0.16; P < .001), and in the subgroup of thrombophilia patients (HR, 0.25; P = .012).
In the thrombophilia group, 6 of the 89 patients (6.7%) who underwent PFO closure had a recurrent event vs 15 of 45 patients (33%) who received medical therapy alone.
The results remained significant when adjusted for possible confounding factors such as age, sex, traditional risk factors (hypertension, diabetes, hypercholesterolemia, and smoking history) and interatrial characteristics (moderate to large shunt size and atrial septal aneurysm).
Of the 46 thrombophilia patients who received medical therapy only, 31 (67.4%) received anticoagulation therapy (14 short-term and 17 lifelong), and 15 patients received antiplatelet therapy.
Recurrent events occurred in 28.6% of those who received short-term anticoagulation, 17.6% of those who received lifelong anticoagulation, and 53.3% of those on antiplatelet therapy.
Time for a Patient-Tailored Therapy
In an accompanying editorial, Julia Seeger, MD, Medical Campus Lake Constance, Friedrichshafen, Germany, and David Hildick-Smith, MD, Royal Sussex County Hospital, Brighton, United Kingdom, conclude that: “The implications for patients with cryptogenic stroke and thrombophilia are clear. These patients are at higher than average risk of recurrent ischemic events. Whether they are treated with percutaneous closure or medical therapy, their elevated risk demonstrates the need for closer follow-up and tailored medical therapy.”
Seeger told Medscape Medical News that “although this is not a randomized trial, it is a very important trial for clinical practice. Thrombophilia patients have been a missing piece of the puzzle regarding PFO closure. Now we have more data showing benefit.”
“These patients with thrombophilia are a very special population with a high risk of embolism who already have an indication for anticoagulation therapy, making it difficult to include them in a randomized trial of PFO closure. But we urgently need data on this group,” she said.
“This study is very good work and shows that PFO closure is beneficial in these patients,” she added. “But even with PFO closure, they are still at higher risk of recurrent stroke and need to be followed very closely.”
Seeger believes that PFO closure should be recommended for thrombophilia patients based on these results. “We can reduce the risk of recurrent strokes in these patients even though their remaining risk is still higher than patients without thrombophilia. They need to be on anticoagulants even after the procedure.”
The study was funded by the National Institutes of Health. The authors and editorialists have disclosed no relevant financial relationships.